New treatments are needed for the 5 to 10 % of severe asthmatics who are not well controlled despite treatment with standard therapy. These severe asthmatics have persistent asthma symptoms and recurrent disease exacerbations despite treatment with high-doses of inhaled corticosteroids plus long-acting &#946;2-agonists or oral corticosteroids. In addition, the utilization of oral corticosteroids are associated with serious and potentially debilitating side effects, such as diabetes, hypertension, weight gain, impaired host defense, reduced bone density, cataracts, skin atrophy, and myopathy. Limited alternative treatment options exist for these severe, refractory asthmatics. This project is investigating whether pharmacological agents that are in use for other disorders can be utilized for the treatment of asthma. In addition, new therapeutic approaches that are in pre-clinical development may be assessed. This project has shown that rapamycin has paradoxical effects on experimental house dust mite-induced asthma and treatment of established asthma exarcerbated airway hyper reactivity and airway inflammation. This suggests that use of rapamycin to inhibit mTORC1 may not be efficacious for the treatment of established house dust mite-induced asthma (PLoS ONE 2012; 7, e33984).